What is the recommended diagnostic work‑up and treatment plan, including surgery, chemotherapy, and maintenance therapy, for a woman in her 60s with newly diagnosed high‑grade serous epithelial ovarian carcinoma?

Management of Newly Diagnosed High-Grade Serous Epithelial Ovarian Carcinoma

For a woman in her 60s with newly diagnosed high-grade serous epithelial ovarian carcinoma, proceed with comprehensive diagnostic staging followed by maximal cytoreductive surgery aiming for no residual disease, then administer 6 cycles of carboplatin (AUC 5-7.5) plus paclitaxel (175 mg/m² every 3 weeks), followed by maintenance therapy with PARP inhibitors and/or bevacizumab based on BRCA/HRD status. 1

Diagnostic Work-Up

Initial Laboratory and Imaging Assessment:

• Serum CA-125 is essential and will be elevated in approximately 85% of advanced disease cases, though only 50% of early-stage cases 1
• Complete blood count with differential and biochemistry for renal and hepatic function 1
• CT scan of chest, abdomen, and pelvis to assess disease extent 1
• Transabdominal and transvaginal ultrasound by an expert examiner 1
• Cytological assessment of pleural effusion if present 1

Critical Diagnostic Consideration: For high-grade serous carcinoma specifically, CA-125 is more reliable than in other subtypes, and measuring CEA or CA 19-9 is unnecessary unless mucinous histology is suspected 1. High-grade serous carcinoma accounts for 70-80% of all epithelial ovarian cancers and presents at advanced stage (III-IV) in up to 95% of cases 2, 3, 4.

Genetic Testing: Given that approximately 20% of high-grade serous carcinomas harbor BRCA1/2 mutations and 25% of ovarian cancer cases overall are hereditary, germline BRCA1/2 testing should be performed in all patients as this directly impacts maintenance therapy decisions 2, 4, 5.

Surgical Management

Comprehensive Surgical Staging by Gynecologic Oncologist:

Surgery must be performed by an appropriately trained gynecologic oncologist with experience in ovarian cancer management 1, 6. The procedure includes:

• Total abdominal hysterectomy and bilateral salpingo-oophorectomy 1, 6
• Infracolic omentectomy 1, 6
• Peritoneal washings for cytological analysis 1, 6
• Systematic biopsies: diaphragmatic peritoneum, paracolic gutters, pelvic peritoneum 1, 6
• Pelvic and para-aortic lymph node sampling or systematic dissection 1, 6
• Maximal cytoreductive effort with the goal of no residual disease (complete macroscopic resection) 1, 6

Surgical Timing Decision: For advanced-stage disease, the choice between primary cytoreductive surgery versus neoadjuvant chemotherapy followed by interval cytoreduction depends on surgical resectability assessment 7. However, primary cytoreduction should be attempted when complete resection appears feasible, as this provides superior outcomes 1, 6.

Common Pitfall: Do not perform fertility-sparing surgery in a woman in her 60s with high-grade serous carcinoma—this aggressive subtype requires complete surgical staging and cytoreduction 1, 2.

Chemotherapy Regimen

Standard First-Line Chemotherapy:

• Carboplatin AUC 5-7.5 mg/ml/min plus paclitaxel 175 mg/m² intravenously over 3 hours every 3 weeks for 6 cycles 1, 6
• This platinum-taxane combination is the established standard for advanced-stage disease 1, 6, 4

For Early-Stage Disease (if applicable): If the patient has stage Ia/Ib poorly differentiated disease or stage Ic/IIA of any grade, adjuvant chemotherapy with either 3 or 6 cycles of carboplatin plus paclitaxel is recommended 1, 6.

Critical Note on Chemoresistance: Approximately 20% of high-grade serous carcinoma patients develop platinum-resistant disease (progression within 6 months of completing platinum therapy), with median survival of only 9-14 months from recurrence 2, 5. Despite initial response rates of 80%, approximately 75% of advanced-stage patients relapse within 2 years 4.

Maintenance Therapy

PARP Inhibitor Maintenance:

• For BRCA1/2-mutated or homologous recombination deficiency (HRD)-positive tumors, PARP inhibitors are indicated as maintenance therapy 2, 3, 5
• BRCA-related high-grade serous carcinoma has approximately 70% five-year overall survival with PARP inhibitor treatment, compared to 10-40% for advanced-stage disease overall 4
• Over 95% of high-grade serous carcinomas have TP53 mutations, making accurate tumor typing critical for PARP inhibitor selection 2, 3

Bevacizumab Maintenance:

• Bevacizumab (anti-angiogenic monoclonal antibody) may be incorporated into maintenance therapy, either alone or in combination with PARP inhibitors 4, 7
• Most patients with advanced-stage disease receive maintenance with bevacizumab and/or PARP inhibitors 4

Treatment Algorithm for Maintenance:

1. If BRCA1/2 mutation or HRD-positive: PARP inhibitor maintenance (with or without bevacizumab) 2, 4, 5
2. If BRCA wild-type and HRD-negative: Consider bevacizumab maintenance 4, 7
3. Molecular testing for HRD status should be performed on tumor tissue to guide this decision 2, 5

Prognosis and Follow-Up Considerations

Expected Outcomes:

• Early-stage disease (I-II): 5-year overall survival of 70-95% with appropriate treatment 4
• Advanced-stage disease (III-IV): 5-year overall survival of 10-40% overall, but up to 70% in BRCA-mutated patients receiving PARP inhibitors 4
• High-grade serous carcinoma is characterized by aggressive behavior with rapid progression 2, 8

Common Pitfall: Do not confuse high-grade serous carcinoma with low-grade serous carcinoma—the latter should NOT receive neoadjuvant chemotherapy as it responds poorly to standard chemotherapy and has more indolent behavior 2. High-grade serous carcinoma requires aggressive platinum-based treatment 2, 5.

Molecular Considerations: The presence of TP53 mutations in over 95% of high-grade serous carcinomas distinguishes this subtype from others and confirms the diagnosis 2, 8. Reversion of BRCA1/2 germline alleles is associated with acquired chemoresistance 5.